Avaliação do perfil clínico e metabólico em resposta ao tratamento com melatonina em pacientes com Transtorno do Espectro Autista
Data
2023-11-24
Autores
Buratto, Eliete Chiconelli Faria 
Orientadores
Amaral, Fernanda Gaspar do
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Caracterizar os pacientes com Transtorno do Espectro Autista quanto ao perfil clínico, padrão de sono, qualidade de vida, perfil metabólico e de concentração urinária noturna da 6-sulfatoximelatonina, além disso, correlacionar esses parâmetros com a concentração do metabólito urinário noturno da melatonina. Ainda, avaliar a resposta terapêutica do uso da melatonina. Métodos: Projeto piloto de ensaio clínico randomizado com 9 pacientes com Transtorno do Espectro Autista com idade entre 10 anos e 16 anos e 11 meses, avaliados nas fases pré e pós-tratamento com melatonina ou placebo (n= 4-5/grupo). Foram realizados anamnese, exame físico geral, escalas e questionários para avaliação do Transtorno do Espectro Autista, do sono, da qualidade de vida, exames séricos relacionados ao metabolismo e análise do metabólito urinário noturno da melatonina. Foi usado o actígrafo por 4 semanas no pré-tratamento e nas últimas 4 semanas no tratamento. Os pacientes foram classificados com ou sem síndrome metabólica e randomizados para a intervenção duplo-cego, com 3 mg de melatonina de ação imediata, no horário entre 20 h e 21h, por 12 semanas. Foram realizadas orientações sobre a melatonina e o sono antes da intervenção para todos os pacientes. Após 8 semanas de tratamento, foi feita a dosagem do metabólito urinário da melatonina na urina noturna e também na segunda urina da manhã. Ao longo da intervenção, contato telefônico semanal foi realizado. Resultados: Houve melhora estatisticamente significativa nas características relacionadas ao Transtorno do Espectro Autista e nos aspectos emocionais da qualidade de vida no grupo melatonina em relação ao pré-tratamento. No grupo placebo, em relação ao pré-tratamento, houve melhora estatisticamente significativa de diversos parâmetros do sono e dos aspectos emocionais da qualidade de vida. Considerando a actigrafia, houve mudança estatisticamente significativa para os pacientes do grupo melatonina que passaram a dormir e acordar mais cedo em relação ao início do estudo. Foi observado redução da pressão arterial sistólica e diastólica, assim como piora no perfil lipídico estatisticamente significativo nos pacientes do grupo melatonina em relação ao pré-tratamento. A resposta do perfil glicídico foi variável e não houve diferença estatisticamente significante no grupo melatonina. O metabólito da melatonina na segunda urina da manhã estava elevado em todos os pacientes que usaram a melatonina. Conclusões: As orientações sobre sono e melatonina podem ter apresentado um efeito positivo sobre a qualidade do sono, aspectos do Transtorno de Espectro Autista e qualidade de vida dos pacientes. O uso da melatonina na pediatria pode ser benéfico não só para parâmetros do sono. Considerando o importante papel da melatonina na fisiologia do metabolismo energético, mais estudos são necessários para estabelecer o efeito do tratamento com melatonina nos parâmetros metabólicos. O aumento dos níveis de 6-sulfatoximelatonina na segunda urina da manhã de todos os pacientes do grupo melatonina indica posologia de uso excessivo e/ou horário inadequado. Essa situação pode causar sonolência excessiva diurna, bem como alterações prejudiciais ao metabolismo. Estudos são necessários para que se estabeleça a dose ideal para o uso da melatonina na pediatria.
Objectives: This study aimed at the characterization of patients with autism spectrum disorder in terms of their clinical, sleep, quality of life, metabolic and nocturnal urinary excretion profiles of 6-sulfatoxymelatonin, and to correlate these parameters with the urinary concentrations of this metabolite. It also evaluated the therapeutic response to the use of melatonin in terms of clinical, sleep, quality of life and metabolic profiles. Methods: This pilot project included 9 patients with autism spectrum disorder aged between 10 years and 16 years and 11 months, who were randomly assigned to placebo or melatonin groups (n= 4-5/group). Anamnesis, general physical examination, scales and questionnaires to assess autism spectrum disorder, sleep, quality of life, serum tests related to metabolism and analysis of the nocturnal urinary metabolite of melatonin were carried out. The actigraphy was used for 4 weeks pre-treatment and for the last 4 weeks of the treatment phase. Patients were classified as having or not metabolic syndrome and then randomized according to this classification. The intervention was double-blind, with 3 mg of immediate-acting melatonin, between 8 p.m. and 9 p.m., for 12 weeks. Guidance on melatonin and sleep was given before the intervention to all the patients. After eight weeks of treatment, the urinary metabolite of melatonin was measured in the night urine and in the second urine of the morning. Throughout the intervention, weekly telephone contact was made with the guardian. Results: There was a statistically significant improvement in the characteristics related to autism spectrum disorder and in the emotional aspects of quality of life in the melatonin group compared to pre-treatment. In the placebo group, compared to pre-treatment, there was a statistically significant improvement in various sleep parameters and emotional aspects of quality of life. Data from actigraphy showed a statistically significant change in which patients in the melatonin group went to bed and woke up earlier than at the start of the study. A reduction in systolic and diastolic blood pressure was observed, as well as a statistically significant worsening of the lipid profile in patients in the melatonin group compared to pre-treatment. The response of the glucose profile was variable and there was no statistically significant difference in the melatonin group. The melatonin metabolite in the second morning urine was elevated in all patients who used melatonin. Conclusions: Guidance on sleep and melatonin may have had a positive effect on sleep quality, aspects of autism spectrum disorder and patients' quality of life. The use of melatonin in pediatrics may be beneficial not only for sleep parameters. Considering the important role of melatonin in metabolic physiology, studies are needed to establish the effect of melatonin treatment on energy metabolism parameters. The increased levels of 6-sulfatoxymelatonin in the second morning urine of all the patients in the melatonin group indicate excessive dosage and/or inappropriate timing. This could lead to excessive daytime sleepiness as well as harmful changes in metabolism. Studies are needed to establish the ideal dose for the use of melatonin in pediatrics.
Objectives: This study aimed at the characterization of patients with autism spectrum disorder in terms of their clinical, sleep, quality of life, metabolic and nocturnal urinary excretion profiles of 6-sulfatoxymelatonin, and to correlate these parameters with the urinary concentrations of this metabolite. It also evaluated the therapeutic response to the use of melatonin in terms of clinical, sleep, quality of life and metabolic profiles. Methods: This pilot project included 9 patients with autism spectrum disorder aged between 10 years and 16 years and 11 months, who were randomly assigned to placebo or melatonin groups (n= 4-5/group). Anamnesis, general physical examination, scales and questionnaires to assess autism spectrum disorder, sleep, quality of life, serum tests related to metabolism and analysis of the nocturnal urinary metabolite of melatonin were carried out. The actigraphy was used for 4 weeks pre-treatment and for the last 4 weeks of the treatment phase. Patients were classified as having or not metabolic syndrome and then randomized according to this classification. The intervention was double-blind, with 3 mg of immediate-acting melatonin, between 8 p.m. and 9 p.m., for 12 weeks. Guidance on melatonin and sleep was given before the intervention to all the patients. After eight weeks of treatment, the urinary metabolite of melatonin was measured in the night urine and in the second urine of the morning. Throughout the intervention, weekly telephone contact was made with the guardian. Results: There was a statistically significant improvement in the characteristics related to autism spectrum disorder and in the emotional aspects of quality of life in the melatonin group compared to pre-treatment. In the placebo group, compared to pre-treatment, there was a statistically significant improvement in various sleep parameters and emotional aspects of quality of life. Data from actigraphy showed a statistically significant change in which patients in the melatonin group went to bed and woke up earlier than at the start of the study. A reduction in systolic and diastolic blood pressure was observed, as well as a statistically significant worsening of the lipid profile in patients in the melatonin group compared to pre-treatment. The response of the glucose profile was variable and there was no statistically significant difference in the melatonin group. The melatonin metabolite in the second morning urine was elevated in all patients who used melatonin. Conclusions: Guidance on sleep and melatonin may have had a positive effect on sleep quality, aspects of autism spectrum disorder and patients' quality of life. The use of melatonin in pediatrics may be beneficial not only for sleep parameters. Considering the important role of melatonin in metabolic physiology, studies are needed to establish the effect of melatonin treatment on energy metabolism parameters. The increased levels of 6-sulfatoxymelatonin in the second morning urine of all the patients in the melatonin group indicate excessive dosage and/or inappropriate timing. This could lead to excessive daytime sleepiness as well as harmful changes in metabolism. Studies are needed to establish the ideal dose for the use of melatonin in pediatrics.